PROCESSES FOR THE PREPARATION OF 4-{8-AMINO-3-[(2S)-1-(BUT-2-YNOYL)-PYRROLIDIN-2-YL]IMIDAZO[1,5-a]-PYRAZIN-1-YL}N-(PYRIDIN-2-YL)-BENZAMIDE

A process for preparing a compound having the structure of Formula (VI):

• or a salt thereof, wherein the process comprises:
• contacting a compound of Formula (IV):
• or a salt thereof, with an acidic medium under conditions sufficient to deprotect the compound of Formula (IV) and form a reaction mixture comprising the compound of Formula (VI), or a salt thereof, and a benzyl halide by-product;
• removing at least a portion of the benzyl halide by-product from the reaction mixture;
• and
• isolating the compound of Formula (VI), or salt thereof, from the reaction mixture under conditions sufficient to substantially avoid the formation of an aminal impurity.

A process for preparing a sulfate salt of a compound having the structure of Formula (IV):

• wherein the process comprises:
• contacting a compound having the structure of Formula (III):
• or a salt thereof, with an aminating agent in a reaction medium to form a reaction mixture comprising the compound of Formula (IV);
• forming a sulfate salt of the compound of Formula (IV);
• and
• isolating the sulfate salt.

A process for preparing a compound having the structure of Formula (II):

• or a salt thereof, wherein the process comprises:
• contacting a compound having the structure of Formula (I):
• or a salt thereof, with a cyclizing agent in the presence of a catalyst in a reaction medium to form the compound of Formula (II), or salt thereof;
• wherein the temperature of the reaction medium is controlled during the contacting step in a manner sufficient to maintain a chiral purity of at least about 80% for the compound of Formula (II), or salt thereof.

A process for preparing a compound having the structure of Formula (III):

• or a salt thereof, wherein the process comprises:
• contacting a compound having the structure of Formula (I):
• or a salt thereof, with a cyclizing agent in the presence of a catalyst in a reaction medium to form a compound of Formula (II):
• or salt thereof;
• and
• brominating the compound of Formula (II), or salt thereof, with a brominating agent to provide a compound having the structure of Formula (III):
• or a salt thereof,
• wherein the temperature of the reaction medium is controlled during the contacting step in a manner sufficient to maintain a chiral purity of at least about 80% for the compound of Formula (II), or salt thereof.